The Origins of Concentric Demyelination: Self-Organization in the Human Brain

Baló's concentric sclerosis is a rare atypical form of multiple sclerosis characterized by striking concentric demyelination patterns. We propose a robust mathematical model for Baló's sclerosis, sharing common molecular and cellular mechanisms with multiple sclerosis. A reconsideration of the analogies between Baló's sclerosis and the Liesegang periodic precipitation phenomenon led us to propose a chemotactic cellular model for this disease. Rings of demyelination appear as a result of self-organization processes, and closely mimic Baló lesions. According to our results, homogeneous and concentric demyelinations may be two different macroscopic outcomes of a single fundamental immune disorder. Furthermore, in chemotactic models, cellular aggressivity appears to play a central role in pattern formation

MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs

Renal modulation: arginine vasopressin and atrial natriuretic peptide

Total body water (TBW) is distributed in compartments divided by semi-permeable membranes. In postnatal life, approximately two thirds of TBW is located in the intracellular space and one third is located in the extracellular space. The latter is further divided with a 3:1 ratio in the interstitial and plasma compartments. Passive equilibration of solutes between body compartments is driven by electrochemical gradients and is mediated by a complex system of transport mechanisms that includes pumps, channels, facilitated carriers and selective paracellular pathways. With few exceptions, water diffuses rapidly across epithelia and cell membranes, following osmotic gradients. High transcellular water transport cannot occur through pure lipid bilayers, as these have low osmotic water permeability ( 3c0.002 cm/s). Water diffusion through cell membranes is therefore mediated by specific water channels, termed aquaporins (AQPs), which enhance osmotic water permeability by 10\u20131000 fold. Because solutes diffuse less rapidly than their solvent, the relative water content of body compartments is primarily regulated by their solute distribution. This allows the organism to adjust its TBW distribution by regulating the activity of solute transporters located in biological membranes that separate body compartments. During early fetal life, TBW represents approximately 90% of body mass. As pregnancy progresses, TBW decreases progressively, to reach 75\u201380% of body mass at the end of gestation. These changes are primarily due to a decline in extracellular water, while intracellular water increases. In the first 24\u201348 h after birth, the extracellular compartment further decreases, as a result of a negative fluid balance in the immediate postnatal period. The fetus constantly regulates its TBW by salt and water exchanges through the placenta membrane. After birth, uptake of water and solutes is limited to gastro-intestinal intakes, while insensible fluid losses increase dramatically. The newborn needs therefore to activate mechanisms that are aimed at controlling water and salt losses. Most of these mechanisms involve the secretion of hormones, which act directly on the kidney. To be efficient, these mechanisms require that sensors, hormone secretion pathways and target organs have reached an appropriate level of maturity. Water excretion or retention is primarily modulated through the regulation of arginine vasopressin (AVP) secretion. Stimulation of thirst has only limited value in newborns, because of their restricted access to free water and immaturity of the central nervous system. Salt retention by the kidney is predominantly achieved by activation of the renin-angiotensin-aldosterone system, which is potentiated by endothelins and adrenergic renal nerve activity. Conversely renal salt losses are stimulated by natriuretic peptides (NPs), prostaglandins, kinins, nitric oxide (NO) and adrenomedullin. In this review, the roles of AVP and NPs in the regulation of body fluid composition during the prenatal and perinatal periods are briefly reviewed. It is important to notice however, that their action is part of a complex network in which all of the above mentioned pathways are synergistically activated or inhibited to maintain body homeostasis

Yeast diversity during tapping and fermentation of palm wine from Cameroon

Abstract In the present study, we have investigated the occurrence of yeast flora during tapping and fermentation of palm wine from Cameroon. The yeast diversity was investigated using both traditional culture-dependent and culture-independent methods. Moreover, to characterize the isolates of the predominant yeast species (Saccharomyces cerevisiae) at the strain level, primers specific for delta sequences and minisatellites of genes encoding the cell wall were used. The results confirm the broad quantitative presence of yeast, lactic acid bacteria and acetic acid bacteria during the palm wine tapping process, and highlight a reduced diversity of yeast species using both dependent and independent methods. Together with the predominant species S. cerevisiae, during the tapping of the palm wine the other species found were Saccharomycodes ludwigii and Zygosaccharomyces bailii. In addition, denaturing gradient gel electrophoresis (DGGE) analysis detected Hanseniaspora uvarum, Candida parapsilopsis, Candida fermentati and Pichia fermentans. In contrast to the progressive simplification of yeast diversity at the species level, the molecular characterization of the S. cerevisiae isolates at the strain level showed a wide intraspecies biodiversity during the different steps of the tapping process. Indeed, 15 different biotypes were detected using a combination of three primer pairs, which were well distributed in all of the samples collected during the tapping process, indicating that a multistarter fermentation takes place in this particular natural, semi-continuous fermentation process